ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. The obtained acetyl-CoA is required for lipid synthesis during membrane biogenesis, as well as for histone acetylation reactions to regulate the expression of certain proteins in aberrantly proliferating cancer cells. Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene. Inhibition of ACLY leads to changes in cancer cell metabolism that promotes tumor growth and proliferation. This review summarizes the role of ACLY in cancer development and its inhibitors in cancer treatment.
The intake of fruits has proven to reduce the risk and incidence of cancer worldwide and plays a crucial role in cancer prevention. Pomegranate (Punica granatum), which belongs to the Punicaceae family, is one such plant that contains beneficial nutrients as well as many bioactive components and important phytochemicals that can be attributed to cancer-related therapeutic purposes. Pomegranate possesses antioxidant, anti-inflammatory, anti-proliferative, anti-angiogenic, anti-invasive, and anti-metastatic properties, and induces apoptosis. It also down-regulates various signaling pathways such as NF-κB, PI3K/AKT/mTOR, and Wnt, and down-regulates the expression of genes that are responsible in cancer development, such as anti-apoptotic genes, MMPs, VEGF, c-met, cyclins, Cdks, and pro-inflammatory cytokines. Therefore, inclusion of the fruit in one's diet would assist in a healthy life protected from cancer and also act as an effective chemotherapeutic with no toxic side effects.
Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I–IV); it can also serve as a prognostic biomarker for oral cancer. Additionally, tobacco carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration; it also induced resistance against cisplatin. Silencing of NGAL activated mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver kinase B1 (LKB1)-activated protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.
BackgroundAccording to GLOBOCAN 2018, oral cancer was reported as the second highest cancer prevalent in India. Despite the several therapies available for oral cancer treatment, tumor recurrence and distant metastasis persist. This study investigates the anticancer potential of Persicaria odorata, commonly known as Vietnamese coriander, used widely in traditional systems of medicine for the treatment of inflammation, stomach ailments, tumors, etc.MethodsThe crude methanolic extract of P. odorata (MPo) was prepared. The anticancer properties of MPo on SAS cells and other human oral squamous cell carcinoma cell line were evaluated using in vitro experimental conditions. The phytochemical constituents present in the MPo were also determined.ResultsPersicaria odorata possesses antiproliferative, antisurvival, antimetastatic activities, and induced cell cycle arrest in the G2 phase. It inhibited Akt-mammalian target of rapamycin (mTOR) signaling pathway and also downregulated the expression of essential proteins that are involved in tumorigenesis such as cyclin D1, cyclooxygenase 2 (COX2), survivin, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). Moreover, the presence of flavonoids and quinones also revealed the anticancer activity of the plant.ConclusionOverall, our study concludes that P. odorata exhibits its anticancer properties through the downregulation of Akt/mTOR signaling pathway in a dose-dependent manner.
Many plants are found to possess reliable pharmacological properties and have started to attract the attention of researchers. One such holistic plant is Acorus calamus, commonly known as sweet flag, belonging to the rhizomatous family Acoraceae. The different parts of this plant, such as the leaves and rhizomes, are used traditionally in different medicinal preparations for the treatment of various ailments including arthritis, neuralgia, diarrhoea, dyspepsia, kidney and liver troubles, eczema, sinusitis, asthma, fevers, bronchitis, hair loss, and other disorders. Many reports have also appeared in mainstream scientific journals confirming its nutritional and medicinal properties. Biochemical analysis of the plant has revealed a large number of secondary metabolites that may be responsible for its rich medicinal properties. Basic scientific research has uncovered the mechanisms by which itexerts its therapeutic effects. Medicinal herbs such as A. calamus are quite promising in the recent therapeutic scenario, with a large number of people favouring remedies and health approaches that are free from the side effects often associated with synthetic chemicals. In this review, we try to summarise the ethno-medicinal uses, botanical descriptions, phytochemical constituents, and biological activity of the plant parts, as well as the molecular targets of A. calamus, which we hope will serve as a good base for further work on this plant.
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